Compounds of the pyridine series



Patented Aug. 2, 1932 UNITED STATES PATENT OFFICE GURT RATE, OF OPLADEN, GERMANY, ASSIGNOR TO THE FIB-M SCHERING-KAI-ILBAUM A. G., OF BERLIN, GERMANY COMPOUNDS on THE PYRIDINE SERIES No Drawing.

My invention refers to new chemical products of therapeutical value and more especially to compounds of the pyridine series containing the OH group in 2-position and halogens in 3 or 5- or in 3 and 5-position.

These compounds which correspond to the general formula:

25 wherein at least one of the two Y is a halogen, while the other may be a halogen or hydrogen and R-COOX a carboxalkyl group, the typical hydrogen atom X of which may also be replaced by an alkali forming metal.

Example 1 17,4 grams 2-oXy-5-bromopyridine are dissolved in 130 ccms. of a 10% caustic soda solution. To this solution is added a solution of 18,8 grams monochloro acetic acid in 20 ccms. water and the mixture is heated to boiling point for live hours. After the solution has cooled down, dilute sulfuric acid is added, the precipitating compound is filtered by 0 suction and dissolved in cold dilute sodium carbonate solution. After filtration to remove the undissolved parts the filtrate is once more precipitated with dilute sulfuric acid. r By recrystallization from water 2-0X0-5- bromopyridine-N-acetic acid is obtained Application filed March 26, 1930. Serial No. 439,221.

forming white coarse crystals melting at 237 238 C. With alkalis the acid forms readily soluble salts. The sodium salt has the formula Example 2 12,7 grams 2-oXy-3,5-dibromopyridine are dissolved in 80 ccms. of a caustic soda solution to which is added a solution of 9,4

grams monochloro acetic acid in 20 ccms' water, the mixture being now heated to boiling point for five hours. After cooling dilute sulfuric acid is added to the solution, the precipitate is filtered by suction and dissolved in cold dilute sodium carbonate solution. The

und'ssolved parts are removed by filtration and the filtrate is once more precipitated with dilute sulfuric acid. By recrystallization from water there is obtained 2-oxo-3, 5-

bromopyridine-N-acetic acid forming small white needles melting at 240241 0., this acid forming with alkali readily soluble salts.

The sodium salt has the formula:-

B Br

tin-000m Example 3 moving the undissolved parts by filtration the filtrate is once more precipitated with dilute sulfuric acid. The 2-oxo-5iodopyridine-N- acetic acid is recrystallized from water in the presence of some animal charcoal. The product thus obtained takes on a brown color at 235 C. and is decomposed at 230 C. With alkalis the acid forms readily soluble salts. The sodium salt has the formula:

I OH2-COONa Example 4 solved in 80 ccms. of a 5%. caustic soda solution to which is added a solution of 4,7 grams monochloro acetic acidin 10 ccms. water, the

mixture being heated to boiling, point for five it hours. After cooling dilute sulfuric acid is added-'to 'the solution,-the precipitate is filtered by suction and dissolved in the cold in dilute soda solution. The undissolved parts are removed by filtration and the filtrate is precipitated once more with dilute sulfuric acid. The 2-oxo-3,5 diiodopyridine-N-acetic acid is recrystallized from a great quantity of water in the presence of animal charcoal. The product takes on a brown color at 237 C. and is decomposed .at 244 C. With alkalis the acid forms readily soluble salts. "The sodiumsalt has the formula dial-000m Example 30 grams 2-oxy-3-bromo5-iodo pyridine are dissolved in 200 ccms. of a caustic soda solution, to which is added a solution of 18,8 grams monochloro acetic acid in ooms. water, the mixture being then heated lute sulfuric acid. Byrecrystallization from water 2-oxo-3-bromo-5-iodo pyridine-N-acet- I ic acid is recovered in the form of small white needles, whichsinter at 237 C. and melt at 244=245 C. With alkalis the acid forms readilysoluble salts. ,The, sodiumsalt has the formula:

I CHr-COONB The increase of solubility of the derivatives,'obtained according to the method above compounds described in the other examples is also increased at least tentimes as comv pared with the starting material; 8,7 grams 2-oxy-3,5-diiodopyridmeare dis- The new compounds are very valuable as contrast agents inthe X-ray examination of the uropoetical system.

Various changes may he made in the de tails disclosed in the foregoing specification without departing from the invention or sacrificing the advantages thereof.

In the-claims affixed to this specification no selection of any particular modification of the invention is intended to the exclusion of other modifications thereof and the right to subsequently make claim to any modification not covered by these claims is expressly reserved.

I claim 1. As new products N-carboxalkylated halogen pyridones having the general formula:

inf Y, Lo i ore-000x is which Y and Y .are hydrogen or halogen atoms, at least one being a halogen atom, and X the typical hydrogen atom which may also be replaced byanalkali forming metal, these compounds being well crystallized colorless substances which dissolve in cold water with difliculty and in hot water more readily and form alkali salts which are very readily soluble in water.

- 2. As new products N-carboxalkylated halogen pyridones having the general formula p Hr-COOX wherein Y is hydrogen ora halogen atom and X the typical hydrogen atom which maalso be replaced byan alkali forming metal: thesecompounds being well crystallized colorless substances which dissolve in cold water 'with difficulty and in hot water more readily and form alkali salts which are very readily soluble in water.

3. As a new product 2-oxo-5-iodo pyridine- N-ac-etic acid having the formula:

JJHa-COOH which dissolves with some difliculty in cold Water and more readily in hot Water and forms very readily soluble alkali salts.

4. As a new product the sodium salt of 2-ox0-5-iodo-pyridine-N-acetic acid having the formula Ifl Hr-GOONa;

In testimony whereof, I affix my signature.

CUBT BATH. 

